1. Field of the Invention
This invention relates to an apparatus and process for using hydrogen peroxide vapor to sterilize articles such as medical instruments, and more particularly to the use of an inorganic hydrogen peroxide complex for such a process.
2. Description of the Related Art
Medical instruments have traditionally been sterilized using either heat, such as is provided by steam, or a chemical, such as formaldehyde or ethylene oxide in the gas or vapor state. Each of these methods has drawbacks. Many medical devices, such as fiber optic devils, endoscopes, power tools, etc. are sensitive to heat, moisture, or both. Formaldehyde and ethylene oxide are both toxic gases that pose a potential hazard to healthcare workers. Problems with ethylene oxide are particularly severe, because its use requires long aeration times to remove the gas from articles that have been sterilized. This makes the sterilization cycle time undesirably long. In addition, both formaldehyde and ethylene oxide require the presence of a substantial amount of moisture in the system. Thus, devices to be sterilized must be humidified before the chemical is introduced or the chemical and moisture must be introduced simultaneously. Moisture plays a role in sterilization with a variety of other chemicals in the gas or vapor state, in addition to ethylene oxide and formaldehyde, as Table 1.
TABLE 1 ______________________________________ Relative Humidity Requirements Literature Chemical for Optimal Efficacy Reference ______________________________________ Ethylene oxide 25-50% 1 Propylene oxide 25-50% 1 Ozone 75-90% 2 Formaldehyde &gt;75% 1 Glutaraldehyde 80-90% 3 Chlorine dioxide 60-80% 4 Methyl bromide 40-70% 1 .beta.-Propiolactone &gt;75% 1 Peracetic acid 40-80% 5 ______________________________________ 1. Bruch, C. W. Gaseous Sterilization, Ann. Rev. Microbiology 15:245-262 (1961). 2. Janssen, D. W. and Schneider, P. M. Overview of Ethylene Oxide Alternative Sterilization Technologies, Zentralsterilisation 1:16-32 (1993). 3. Bovallius, A. and Anas, P. SurfaceDecontaminating Action of Glutaraldehyde in the GasAerosol Phase. Applied and Environmental Microbiology, 129-134 (Aug. 1977). 4. Knapp, J. E. et al. Chlorine Dioxide As a Gaseous Sterilant, Medical Device & Diagnostic Industry, 48-51 (Sept. 1986). 5. Portner, D. M. and Hoffman, R. K. Sporicidal Effect of Peracetic Acid Vapor, Applied Microbiology 16:1782-1785 (1968).
Sterilization using hydrogen peroxide vapor has been shown to have some advantages over other chemical sterilization processes (see, e.g., U.S. Pat. Nos. 4,169,123 and 4,169,124), and the combination of hydrogen peroxide with a plasma provides additional advantages, as disclosed in U.S. Pat. No. 4,643,876. In these disclosures the hydrogen peroxide vapor is generated from an aqueous solution of hydrogen peroxide, which ensures that there is moisture present in the system. These disclosures, together with those summarized in Table 1, teach that moisture is required for hydrogen peroxide in the vapor phase to be effective or to exhibit its maximum sporicidal activity. However, the use of aqueous solutions of hydrogen peroxide to generate hydrogen peroxide vapor for sterilization may cause problems. At higher pressures, such as atmospheric pressure, excess water in the system can cause condensation. Thus, one must reduce the relative humidity in a sterilization enclosure before introducing the aqueous hydrogen peroxide vapor.
The sterilization of articles containing diffusion-restricted areas, such as long narrow lumens, presents a special challenge for hydrogen peroxide vapor that has been generated from an aqueous solution of hydrogen peroxide, because:
1. Water has a higher vapor pressure than hydrogen peroxide and will vaporize faster than hydrogen peroxide from an aqueous solution. PA1 2. Water has a lower molecular weight than hydrogen peroxide and will diffuse faster than hydrogen peroxide in the vapor state.
Because of this, when an aqueous solution of hydrogen peroxide is vaporized, the water reaches the items to be sterilized first and in higher concentration. The water vapor therefore becomes a barrier to the penetration of hydrogen peroxide vapor into diffusion restricted areas, such as small crevices and long narrow lumens. One cannot solve the problem by removing water from the aqueous solution and using more concentrated hydrogen peroxide, since concentrated solutions of hydrogen peroxide, i.e., greater than 65% by weight, can be hazardous, due to the oxidizing nature of the solution.
U.S. Pat. Nos. 4,642,165 and 4,744,951 attempt to solve this problem. The former discloses metering small increments of a hydrogen peroxide solution onto a heated surface to ensure that each increment is vaporized before the next increment is added. Although this helps to eliminate the difference in the vapor pressure and volatility between hydrogen peroxide and water, it does not address the fact that water diffuses faster than hydrogen peroxide in the vapor state.
The latter patent describes a process for concentrating hydrogen peroxide from a relatively dilute solution of hydrogen peroxide and water and supplying the concentrated hydrogen peroxide in vapor form to a sterilization chamber. The process involves vaporizing a major portion of the water from the solution and removing the water vapor produced before injecting the concentrated hydrogen peroxide vapor into the sterilization chamber. The preferred range for the concentrated hydrogen peroxide solution is 50% to 80% by weight. This process has the disadvantage of working with solutions that are in the hazardous range; i.e., greater than 65% hydrogen peroxide, and also does not remove all of the water from the vapor state. Since water is still present in the solution, it will vaporize first, diffuse faster, and reach the items to be sterilized first. This effect will be especially pronounced in long narrow lumens.
U.S. Pat. No. 4,943,414 discloses a process in which a vessel containing a small amount of a vaporizable liquid sterilant solution is attached to a lumen, and the sterilant vaporizes and flows directly into the lumen of the article as the pressure is reduced during the sterilization cycle. This system has the advantage that the water and hydrogen peroxide vapor are pulled through the lumen by the pressure differential that exists, increasing the sterilization rate for lumens, but it has the disadvantage that the vessel needs to be attached to each lumen to be sterilized. In addition, water is vaporized faster and precedes the hydrogen peroxide vapor into the lumen.
U.S. Pat. No. 5,008,106 discloses that a substantially anhydrous complex of PVP and H.sub.2 O.sub.2 is useful for reducing the microbial content of surfaces. The complex, in the form of a fine white powder, is used to form antimicrobial solutions, gels, ointments, etc. It can also be applied to gauze, cotton swabs, sponges and the like. The H.sub.2 O.sub.2 is released upon contact with water present on the surfaces containing the microbes. Thus, this method too requires the presence of moisture to effect sterilization.
Certain inorganic hydrogen peroxide complexes have been reported including examples within the following classes: alkali metal and ammonium carbonates, alkali metal oxalates, alkali metal phosphates, alkali metal pyrophosphates, fluorides and hydroxides. U.S.S.R. patent document No. SU 1681860 (Nikolskaya et al.) discloses that surfaces can be decontaminated, although not necessarily sterilized, using ammonium fluoride peroxohydrate (NH.sub.4 F.H.sub.2 O.sub.2). However, this inorganic peroxide complex provides decontamination only within the very narrow temperature range of 70.degree.-86.degree. C. Even within this range, decontamination times were quite long, requiring at least two hours. Additionally, it is known that ammonium fluoride decomposes to ammonia and hydrofluoric acid at temperatures above 40.degree. C. Due to its toxicity and reactivity, hydrofluoric acid is undesirable in most sterilization systems. Moreover, Nikolskaya et al. disclose that despite the release of 90% of its hydrogen peroxide at 60.degree. C., NH.sub.4 F.H.sub.2 O.sub.2 is ineffective at decontamination of surfaces at this temperature. Thus, it appears that a factor other than hydrogen peroxide is responsible for the decontamination noted.
Hydrogen peroxide is capable of forming complexes with both organic and inorganic compounds. The binding in these complexes is attributed to hydrogen bonding between electron rich functional groups in the complexing compound and the peroxide hydrogen. The complexes have been used in commercial and industrial applications such as bleaching agents, disinfectants, sterilizing agents, oxidizing reagents in organic synthesis, and catalysts for free-radical-induced polymerization reactions.
Generally, these types of compounds have been prepared by the crystallization of the complex from an aqueous solution. For example, urea hydrogen peroxide complex was prepared by Lu et al. (J. Am. Chem. Soc.63(1):1507-1513 (1941)) in the liquid phase by adding a solution of urea to a solution of hydrogen peroxide and allowing the complex to crystallize under the proper conditions. U.S. Pat. No. 2,986,448 describes the preparation of sodium carbonate hydrogen peroxide complex by treating a saturated aqueous solution of Na.sub.2 CO.sub.3 with a solution of 50 to 90% H.sub.2 O.sub.2 in a closed cyclic system at 0.degree. to 5.degree. C. for 4 to 12 hours. More recently, U.S. Pat. No. 3,870,783 discloses the preparation of sodium carbonate hydrogen peroxide complex by reacting aqueous solutions of hydrogen peroxide and sodium carbonate in a batch or continuous crystallizer. The crystals are separated by filtration or centrifugation and the liquors used to produce more sodium carbonate solution. Titova et al. (Zhurnal Neorg. Khim., 30:2222-2227, 1985) describe the synthesis of potassium carbonate peroxyhydrate (K.sub.2 CO.sub.3. 3H.sub.2 O.sub.2) by reaction of solid potassium carbonate with an aqueous solution of hydrogen peroxide at low temperature followed by crystallization of the complex from ethanol. These methods work well for peroxide complexes that form stable, crystalline free-flowing products from aqueous solution.
U.S. Pat. Nos. 3,376,110 and 3,480,557 disclose the preparation of a complex of hydrogen peroxide with a polymeric N-vinylheterocyclic compound (PVP) from aqueous solution. The resultant complexes contained variable amounts of hydrogen peroxide and substantial amounts of water. U.S. Pat. No. 5,008,093 teaches that free-flowing, stable, substantially anhydrous complexes of PVP and H.sub.2 O.sub.2 could be obtained by reacting a suspension of PVP and a solution of H.sub.2 O.sub.2 in an anhydrous organic solvent like ethyl acetate. More recently, U.S. Pat. No. 5,077,047 describes a commercial process for producing the PVP-hydrogen peroxide product by adding finely divided droplets of a 30% to 80% by weight aqueous solution of hydrogen peroxide to a fluidized bed of PVP maintained at a temperature of ambient to 60.degree. C. The resultant product was found to be a stable, substantially anhydrous, free flowing powder with a hydrogen peroxide concentration of 15 to 24%.
U.S. Pat. No. 5,030,380 describes the preparation of a solid polymeric electrolytic complex with hydrogen peroxide by first forming a complex in aqueous solution and then drying the reaction product under vacuum or by spray drying at a low enough temperature to avoid thermal degradation of the product.
All of these previous methods of preparing hydrogen peroxide complexes use solutions of hydrogen peroxide. Either the complex is formed in a solution containing hydrogen peroxide or droplets of a hydrogen peroxide solution are sprayed onto a fluidized bed of the reactant material.
Vapor phase and gas phase reactions are well known synthesis methods. For example, U.S. Pat. No. 2,812,244 discloses a solid-gas process for dehydrogenation, thermal cracking, and demethanation. Fujimoto et al. (J. Catalysis, 133:370-382 (1992)) described a vapor-phase carboxylation of methanol. Zellers et al. (Anal. Chem., 62:1222-1227 (1990)) discussed the reaction of styrene vapor with a square-plannar organoplatinum complex. These prior art vapor- and gas-phase reactions, however, were not used to form hydrogen peroxide complexes.